For over 15 years the central importance of "perivascular cells" in a variety of neuroimmunological reactions has been recognized. Despite the roles they apparently play in a spectrum of physiological and neuropathological conditions, their exact nature and range of functional possibilities has not been extensively analyzed. Depending on the situation, the perivascular cell can exhibit properties resembling microglial cells, dendritic cells or regular macrophages. This laboratory has a longstanding and productive interest in this resident CNS cell type. In this proposal we wish to define the nature of the perivascular cell more completely. In doing so we will test two hypotheses: (a) that perivascular cells are facultative dendritic cells and possess potential not found in differentiated tissue macrophages; and (b) that these cells are central control elements in governing neural inflammation and CNS immunological activation. Another important and recent discovery is the important, central role of IL-23 in the production of tissue specific inflammation mediated by T cells. In the CNS perivascular cells have receptors for this cytokine and may synthesize it when stimulated. Thus, the role of IL-23 vis-a-vis perivascular cells will also be studied. The proposed investigations will be done through experiments under three specific aims. #1 is to examine the phenotype and products of perivascular cells isolated from the rat CNS. #2 is to determine if PVCs function in distinct ways between divers rat strains that differ relative to their ability to develop CNS inflammation. I1-23 may change this phenotypic difference, or underlie it. #3 is to study the response of PVCs when they confront and present antigen to fully activated T lymphocytes. This is the situation that actually occurs when T cell mediated inflammation is caused in the CNS. As a group, these investigations should more completely elucidate the role of perivascular cells in health and disease, and their relationship to IL-23.